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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
2005-1-4
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pubmed:abstractText |
Nuclear factor E2 p45-related factor 2 (NRF2) contributes to cellular protection against oxidative insults and chemical carcinogens via transcriptional activation of antioxidant/detoxifying enzymes. To understand the molecular basis of NRF2-mediated protection against oxidative lung injury, pulmonary gene expression profiles were characterized in Nrf2-disrupted (Nrf2(-/-)) and wild-type (Nrf2(+/+)) mice exposed to hyperoxia or air. Genes expressed constitutively higher in Nrf2(+/+) mice than in Nrf2(-/-) mice included antioxidant defense enzyme and immune cell receptor genes. Higher basal expression of heat shock protein and structural genes was detected in Nrf2(-/-) mice relative to Nrf2(+/+) mice. Hyperoxia enhanced expression of 175 genes (> or = twofold) and decreased expression of 100 genes (> or =50%) in wild-type mice. Hyperoxia-induced upregulation of many well-known/new antioxidant/defense genes (e.g., Txnrd1, Ex, Cp-2) and other novel genes (e.g., Pkc-alpha, Tcf-3, Ppar-gamma) was markedly greater in Nrf2(+/+) mice than in Nrf2(-/-) mice. In contrast, induced expression of genes encoding extracellular matrix and cytoskeletal proteins was higher in Nrf2(-/-) mice than in Nrf2(+/+) mice. These NRF2-dependent gene products might have key roles in protection against hyperoxic lung injury. Results from our global gene expression profiles provide putative downstream molecular mechanisms of oxygen tissue toxicity.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0891-5849
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
38
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
325-43
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:15629862-Animals,
pubmed-meshheading:15629862-Antioxidants,
pubmed-meshheading:15629862-Atmosphere Exposure Chambers,
pubmed-meshheading:15629862-DNA-Binding Proteins,
pubmed-meshheading:15629862-Gene Expression Profiling,
pubmed-meshheading:15629862-Hyperoxia,
pubmed-meshheading:15629862-Immunohistochemistry,
pubmed-meshheading:15629862-Lung,
pubmed-meshheading:15629862-Mice,
pubmed-meshheading:15629862-Mice, Inbred ICR,
pubmed-meshheading:15629862-Mice, Knockout,
pubmed-meshheading:15629862-Models, Biological,
pubmed-meshheading:15629862-NF-E2-Related Factor 2,
pubmed-meshheading:15629862-Nuclear Proteins,
pubmed-meshheading:15629862-Oxygen,
pubmed-meshheading:15629862-RNA, Messenger,
pubmed-meshheading:15629862-Time Factors,
pubmed-meshheading:15629862-Trans-Activators
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pubmed:year |
2005
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pubmed:articleTitle |
Gene expression profiling of NRF2-mediated protection against oxidative injury.
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pubmed:affiliation |
Department of Environmental Health Sciences, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21205, USA. cho2@niehs.nih.gov
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, U.S. Gov't, P.H.S.,
Research Support, N.I.H., Extramural
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